The Gut-Brain Axis

Written by Charlotte Green

Scientific research has shown that there exists a bidirectional communication system between the gut and brain and is commonly referred to as the gut-brain axis. The nervous system can control gut functions, whereas signalling in the gastro-intestinal tract can also affect the brain, including influencing cognition and mood.1 Emerging evidence suggests that the gut microbiota is an essential mediator in gut-brain communication. The gut microbiota is the community of trillions of micro-organisms residing mainly in the large intestine, with most species working symbiotically to maintain our health.2 Colonisation begins at birth and is subsequently influenced by environmental factors such as geography, diet, stress and physical activity levels.3 Thus, an individual’s unique gut microbiota composition can influence their brain health via the gut-brain axis.


How do the gut and brain communicate?


Signalling between the gut and brain can occur via the vagus nerve, the main nerve of the parasympathetic nervous system. Branches of the vagus nerve connect the gastro-intestinal tract to networks in the brain important for emotional regulation.4 This system is heavily influenced by the gut microbiota as the vagus nerve can sense gut microbial metabolites such as short chain fatty acids (SCFAs).5 SCFAs are important mediators of anti-inflammatory pathways and can protect the brain from inflammatory-induced neuronal damage, which has been linked to depression.6


Furthermore, serotonin, our so called “happy hormone”, is one of the most important signalling molecules in the gut-brain axis. In fact, the majority of the serotonin found in the body is made in the gastro-intestinal tract. The gut microbiota can influence serotonin biosynthesis by regulating the availability of dietary tryptophan, the major component of serotonin.7 The gut microbiota can also directly produce other neurotransmitters such as GABA, however evidence is limited on the amount of gut microbiota-synthesised GABA that is able to enter the brain and influence its function.8


The Gut-Brain Axis in Health and Disease


Abnormal functioning of the gut-brain axis is associated with diseases affecting both the digestive system and the brain.

  • Those with irritable bowel syndrome (IBS), the most common gut-brain disorder, are more likely to have anxiety disorders and visa versa. In fact, in those with both IBS and anxiety, IBS often developed first, suggesting gut dysfunction could play a part in the development of mood disorders.4

  • The gut microbiota could affect the development of depression, as studies have noted that those diagnosed with depression have a less diverse gut microbiota composition.9 This could be due to increased inflammation from bacterial products10 that can cause neuronal damage, increasing the risk of depression.6

  • Dysregulation of the gut-brain axis could be important for the development of neurodegenerative diseases, including Alzheimer’s disease. Gut microbiota dysbiosis, characterised by a shift to a pro-inflammatory community, has been associated with Alzheimer’s disease.11 This can cause systemic inflammation, including in the brain, leading to the accelerated aggregation of amyloid-b plaques, the defining feature of Alzheimer’s disease, and progressive neurodegeneration.12

Dietary Considerations


The diet is a significant factor influencing the composition of the gut microbiota, meaning it is important for ensuring the optimal function of the gut-brain axis. The key is gut microbiota diversity, to ensure a range of bacterial species can carry out a variety of functions. This can be achieved by including a wide range of different plant-based foods.3 Including sources of prebiotics, a type of fibre found in foods such as bananas, leeks, onions and oats, is particularly important because they act as fuel for the microbiota. This allows the beneficial species to grow and thrive.13 However, a diet high in ultra-processed foods, such as pre-packaged snacks, confectionary, and ready-meals, has been linked to reduced gut microbial diversity, largely due to a lack of fibre.14


Evidence suggests that a Mediterranean-style diet could be particularly helpful to ensure the normal function of the gut-brain axis. The influential SMILES trial successfully utilised a 12-week Mediterranean diet as an adjuvant therapy for clinical depression. The study showed a significant reduction in depressive symptoms in the diet group compared to a group receiving social support.15 The Mediterranean diet is a largely plant-focused diet, abundant in fruits, vegetables, wholegrains nuts, seeds, extra-virgin olive oil, alongside regular fish consumption, a rich source of omega-3 fatty acids. The high levels of dietary fibre nourish the gut microbiota16 and polyphenol-rich foods such as berries, red wine and extra virgin olive oil, act as anti-inflammatories to protect brain function.17


References


1. Dinan, T. G., Cryan, J. F., Dinan, T. G., Cryan, J. F. & Physiol, J. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J. Physiol. 595, 489–503 (2017).


2. Adak, A. & Khan, M. R. An insight into gut microbiota and its functionalities. Cellular and Molecular Life Sciences vol. 76 473–493 (2019).


3. Gentile, C. L. & Weir, T. L. The gut microbiota at the intersection of diet and human health. Science vol. 362 776–780 (2018).


4. Margolis, K. G., Cryan, J. F. & Mayer, E. A. The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology160, 1486–1501 (2021).


5. Bonaz, B., Bazin, T. & Pellissier, S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front. Neurosci. 12, 49 (2018).


6. Lassale, C. et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Mol. Psychiatry 24, 965–986 (2019).


7. Yano, J. M. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell161, 264–276 (2015).


8. Strandwitz, P. Neurotransmitter modulation by the gut microbiota. Brain Res. 1693, 128–133 (2018).


9. Butler, M. I., Mörkl, S., Sandhu, K. V., Cryan, J. F. & Dinan, T. G. The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale : que Devrions-Nous dire à nos Patients? Can. J. Psychiatry. 64, 747–760 (2019).


10. Wang, B., Yao, M., Lv, L., Ling, Z. & Li, L. The Human Microbiota in Health and Disease. Engineering 3, 71–82 (2017).


11. Vogt, N. M. et al. Gut microbiome alterations in Alzheimer’s disease. Sci. Reports 2017 71 7, 1–11 (2017).


12. Goyal, D., Ali, S. A. & Singh, R. K. Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 106, (2021).


13. Davani-Davari, D. et al. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods vol. 8 (2019).


14. Shi, H. et al. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. Microbiome 9, (2021).


15. FN, J. et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 15, (2017).


16. Tosti, V., Bertozzi, B. & Fontana, L. Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. Journals of Gerontology - Series A Biological Sciences and Medical Sciences vol. 73 318–326 (2018).


17. Muñoz, M. A., Fíto, M., Marrugat, J., Covas, M. I. & Schröder, H. Adherence to the Mediterranean diet is associated with better mental and physical health. Br. J. Nutr. 101, 1821–1827 (2009).

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